Acute effects of rapamycin on glomerular dynamics: a micropuncture study in the rat

The acute effects of cyclosporin (CsA, 20 mg(kg i.v.) and rapamycin (RAPA, 5 mg(kg i.v.) on glomerular dynamics were separately investigated by renal micropuncture in two groups of intact rats (group CsA and RAPA, respectively) and compared with vehicle-treated rats, used as controls (group CON). Left kidney glomerular filtration rate (GFR) was decreased by CSA (-35% vs. CON, P<0.05), but was not affected by RAPA (-14% vs. CON, NS), whereas the single-nephron GFR (SNGFR) was significantly decreased in both groups (-40% in CsA, P<0.01 and -26% in RAPA, P<0.05 vs. CON). In both groups glomerular plasma flow (GPF) was significantly reduced vs. CON (CsA: -48%, and RAPA: -25%) due to the increase in both afferent (Ra) and efferent (Re) glomerular resistances: group CSA showed a prevalent rise in Re (+98% vs. CON, P<0.001) than in Ra (+66%, P<0.001); in group RAPA the increment was modest and similar in Ra and Re (+33 and +32%, respectively, NS versus CON). A further group of rats was studied in which L-Arginine (ARG), the precursor of nitric oxide (NO), was administered (2.5 mg/Kg/min iv) with RAPA (group ARG). ARG limited the rise in Ra and Re, thereby preserving GPF; nevertheless, SNGFR remained low (-26% vs. CON, P<0.05) due to the decrease in the effective filtration pressure (-26% vs. CON). These data demonstrate that: (1) CsA is nephrotoxic at immunosuppressive doses; (2) RAPA, even at huge doses, has marginal effects on renal and glomerular dynamics; (3) the ARG-NO pathway is only partially involved in the vasoconstriction of superficial nephrons after RAPA administration.     

Management of respiratory complications and rehabilitation in individuals with muscular dystrophies: 1st Consensus Conference report from UILDM - Italian Muscular Dystrophy Association (Milan,January 25-26, 2019)

Respiratory complications are common in the patient with muscular dystrophy. The periodic clinical and instrumental respiratory evaluation is extremely important. Despite the presence in the literature of updated guidelines, patient associations often report lack of knowledge of these pathologies, particularly in peripheral hospitals. The purpose of this work, inspired by the Italian Muscular Dystrophy Association (UILDM) is to improve management of respiratory problems necessary for the management of these patients complex. To this end, the main items that the specialist can meet in the follow-up of these pathologies have been analyzed and discussed, among which the respiratory basal evaluation, the criteria of adaptation to non-invasive ventilation, management of bronchial secretions, situations of respiratory emergency, indications for tracheostomy and the subject of advance directives of treatment (DAT).Key words: respiratory failure, muscular dystrophy, cough efficacy, spirometry, polygraphy, non-invasive ventilation, arterial blood gases, cough machine, invasive ventilation, tracheostomy, mechanical ventilation     

Gene expression changes in dorsal root ganglia following peripheral nerve injury: roles in inflammation,cell death and nociception

Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, cell death and nociception, and highlights how alterations in their gene expression within the dorsal root ganglia can affect functional recovery. The majority of studies used polymerase chain reaction within animal models to analyse the dynamic changes following peripheral nerve injuries. This review aims to highlight the factors at the gene expression level that impede functional recovery and are hence are potential targets for therapeutic approaches. Where possible the experimental model, specific time-points and cellular location of expression levels are reported.     

Validity and reliability of the Unified Classification System applied to periprosthetic femur fractures: a comparison with the Vancouver system

Abstract

Objective: The Unified Classification System (UCS) presents itself as an evolution of the Vancouver Classification (VCS) for the evaluation of periprosthetic fractures of the proximal femur (PPF). The aim of our study was to highlight any loss of reproducibility or validity of the new classification system, compared to the previous one.

Material and methods: We tested the interobserver and intraobserver agreement using 40 PPF clinical cases. Each classifying subtype of the UCS and VCS was present in at least two cases. Six experienced hip surgeons (Senior Surgeon, SS) and 5 surgeons in training (Junior Surgeon, JS) classified the clinical cases, using VCS and UCS. The validity of both classifications was then tested with intraoperative surveys.

Results: The mean κ value for interobserver agreement for the VCS in the JS group was 0.65 and 0.81 for the SS group. The mean κ value for interobserver agreement for the UCS in the JS group was 0.63 and 0.65 for the SS group. The mean κ value for intraobserver agreement for the VCS in the JS group was 0.71 and 0.73 for the SS group. The mean κ value for intraobserver agreement for the UCS in the JS group was 0.72 and 0.7 for the SS group. Validity analysis showed a moderate agreement for the VCS and a good agreement for the UCS.

Conclusion: The UCS completes the Vancouver classification, expanding it. It is reliable, despite the increase in classification categories and number of parameters to evaluate, with a slightly higher validity.